Learning the language of antibody hypervariability.

Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose "foundational" PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody Mutagenesis-Augmented Processing (AbMAP), which fine-tunes foundational models for antibody-sequence inputs by supervising on antibody structure and binding specificity examples.

Modular DNA origami-based electrochemical detection of DNA and proteins.

The diversity and heterogeneity of biomarkers has made the development of general methods for single-step quantification of analytes difficult. For individual biomarkers, electrochemical methods that detect a conformational change in an affinity binder upon analyte binding have shown promise. However, because the conformational change must operate within a nanometer-scale working distance, an entirely new sensor, with a unique conformational change, must be developed for each analyte.

CRISPR-Enabled Autonomous Transposable Element (CREATE) for RNA-based gene editing and delivery.

To address a wide range of genetic diseases, genome editing tools that can achieve targeted delivery of large genes without causing double-strand breaks (DSBs) or requiring DNA templates are necessary. Here, we introduce CRISPR-Enabled Autonomous Transposable Element (CREATE), a genome editing system that combines the programmability and precision of CRISPR/Cas9 with the RNA-mediated gene insertion capabilities of the human LINE-1 (L1) element. CREATE employs a modified L1 mRNA to carry a payload gene, and a Cas9 nickase to facilitate targeted editing by L1-mediated reverse transcription and integration without relying on DSBs or DNA templates.

Taurine prevents mitochondrial dysfunction and protects mitochondria from reactive oxygen species and deuterium toxicity.

Taurine, although not a coding amino acid, is the most common free amino acid in the body. Taurine has multiple and complex functions in protecting mitochondria against oxidative-nitrosative stress. In this comprehensive review paper, we introduce a novel potential role for taurine in protecting from deuterium (heavy hydrogen) toxicity.

Prevalence of Borrelia burgdorferi sensu lato infection in the Czech Republic.

Introduction: Lyme borreliosis (LB), an infection caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. To further characterize the LB burden in the Czech Republic, we conducted a seroprevalence study and estimated the incidence of symptomatic Bbsl infections.

Methods: Anti-Bbsl IgM and IgG antibodies were detected in sera collected from the adult population in 2011 -2012 by enzyme-linked immunosorbent assay and immunoblot tests at the National Reference Laboratory.

Integrating microfluidic and bioprinting technologies: advanced strategies for tissue vascularization.

Tissue engineering offers immense potential for addressing the unmet needs in repairing tissue damage and organ failure. Vascularization, the development of intricate blood vessel networks, is crucial for the survival and functions of engineered tissues. Nevertheless, the persistent challenge of ensuring an ample nutrient supply within implanted tissues remains, primarily due to the inadequate formation of blood vessels.

A case study on using a large language model to analyze continuous glucose monitoring data.

Continuous glucose monitors (CGM) provide valuable insights about glycemic control that aid in diabetes management. However, interpreting metrics and charts and synthesizing them into linguistic summaries is often non-trivial for patients and providers. The advent of large language models (LLMs) has enabled real-time text generation and summarization of medical data.

The prognosis for delayed immune recovery in HIV-infected children might be associated with pre-cART CD4 T cell count irrespective of co-infection with tuberculosis.

Background: Immune reconstitution following the initiation of combination antiretroviral therapy (cART) significantly impacts the prognosis of individuals infected with human immunodeficiency virus (HIV). Our previous studies have indicated that the baseline CD4 T cells count and percentage before cART initiation are predictors of immune recovery in TB-negative children infected with HIV, with TB co-infection potentially causing a delay in immune recovery. However, it remains unclear whether these predictors consistently impact immune reconstitution during long-term intensive cART treatment in TB-negative/positive children infected with HIV.

Individualized temporal patterns drive human sleep spindle timing.

Sleep spindles are cortical electrical oscillations considered critical for memory consolidation and sleep stability. The timing and pattern of sleep spindles are likely to be important in driving synaptic plasticity during sleep as well as preventing disruption of sleep by sensory and internal stimuli. However, the relative importance of factors such as sleep depth, cortical up/down-state, and temporal clustering in governing sleep spindle dynamics remains poorly understood.

Role of the stratosphere in the global mercury cycle.

Mercury (Hg) is a global pollutant with substantial risks to human and ecosystem health. By upward transport in tropical regions, mercury enters into the stratosphere, but the contribution of the stratosphere to global mercury dispersion and deposition remains unknown. We find that between 5 and 50% (passing through the 400-kelvin isentropic surface and tropopause, respectively) of the mercury mass deposited on Earth's surface is chemically processed in the lower stratosphere.

Thickness-dependent polaron crossover in tellurene.

Polarons, quasiparticles from electron-phonon coupling, are crucial for material properties including high-temperature superconductivity and colossal magnetoresistance. However, scarce studies have investigated polaron formation in low-dimensional materials with phonon polarity and electronic structure transitions. In this work, we studied polarons of tellurene, composed of chiral Te chains.

Domain Adversarial Convolutional Neural Network Improves the Accuracy and Generalizability of Wearable Sleep Assessment Technology.

Wearable accelerometers are widely used as an ecologically valid and scalable solution for long-term at-home sleep monitoring in both clinical research and care. In this study, we applied a deep learning domain adversarial convolutional neural network (DACNN) model to this task and demonstrated that this new model outperformed existing sleep algorithms in classifying sleep-wake and estimating sleep outcomes based on wrist-worn accelerometry. This model generalized well to another dataset based on different wearable devices and activity counts, achieving an accuracy of 80.

Advances in 2D Molybdenum Disulfide Transistors for Flexible and Wearable Electronics.

As the trajectory of developing advanced electronics is shifting towards wearable electronics, various methods for implementing flexible and bendable devices capable of conforming to curvilinear surfaces have been widely investigated. In particular, achieving high-performance and stable flexible transistors remains a significant technical challenge, as transistors are fundamental components of electronics, playing a key role in overall performance. Among the wide range of candidates for flexible transistors, two-dimensional (2D) molybdenum disulfide (MoS)-based transistors have emerged as potential solutions to address these challenges.

Advancing 3D Engineered In Vitro Models for Heart Failure Research: Key Features and Considerations.

Heart failure is characterized by intricate myocardial remodeling that impairs the heart's pumping and/or relaxation capacity, ultimately reducing cardiac output. It represents a major public health burden, given its high prevalence and associated morbidity and mortality rates, which continue to challenge healthcare systems worldwide. Despite advancements in medical science, there are no treatments that address the disease at its core.

Opening the AI Black Box: Distilling Machine-Learned Algorithms into Code.

Can we turn AI black boxes into code? Although this mission sounds extremely challenging, we show that it is not entirely impossible by presenting a proof-of-concept method, MIPS, that can synthesize programs based on the automated mechanistic interpretability of neural networks trained to perform the desired task, auto-distilling the learned algorithm into Python code. We test MIPS on a benchmark of 62 algorithmic tasks that can be learned by an RNN and find it highly complementary to GPT-4: MIPS solves 32 of them, including 13 that are not solved by GPT-4 (which also solves 30). MIPS uses an integer autoencoder to convert the RNN into a finite state machine, then applies Boolean or integer symbolic regression to capture the learned algorithm.

Age- and Sex-Based Developmental Biomarkers in Eye Movements.

Background: Eye movement research serves as a critical tool for assessing brain function, diagnosing neurological and psychiatric disorders, and understanding cognition and behavior. Sex differences have largely been under reported or ignored in neurological research. However, eye movement features provide biomarkers that are useful for disease classification with superior accuracy and robustness compared to previous classifiers for neurological diseases.

MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction.

MicroRNA (miR: small noncoding RNA)-150 is evolutionarily conserved and is downregulated in patients with diverse forms of heart failure (HF) and in multiple mouse models of HF. Moreover, miR-150 is markedly correlated with the outcome of patients with HF. We previously reported that systemic or cardiomyocyte-derived miR-150 in mice elicited myocardial protection through the inhibition of cardiomyocyte death, without affecting neovascularization and T cell infiltration.

Exploring the Dynamics of Canine-Assisted Interactions: A Wearable Approach to Understanding Interspecies Well-Being.

Canine-assisted interactions (CAIs) have been explored to offer therapeutic benefits to human participants in various contexts, from addressing cancer-related fatigue to treating post-traumatic stress disorder. Despite their widespread adoption, there are still unresolved questions regarding the outcomes for both humans and animals involved in these interactions. Previous attempts to address these questions have suffered from core methodological weaknesses, especially due to absence of tools for an efficient objective evaluation and lack of focus on the canine perspective.

UTX Epigenetically Imposes a Cytolytic Effector Program in Autoreactive Stem-like CD8+ T cell Progenitors.

Type 1 Diabetes Mellitus (T1D) is an autoimmune disease caused by unremitting immune attack on pancreas insulin-producing beta cells. Persistence of the autoimmune response is mediated by TCF1+ Ly108+ progenitor CD8+ T (T) cells, a stem-like population that gives rise to exhausted effectors with limited cytolytic function in chronic virus infection and cancer. What paradoxically drives T conversion to highly cytolytic effectors in T1D, however, remains unclear.

Sampling Mars: Geologic context and preliminary characterization of samples collected by the NASA Mars 2020 Perseverance Rover Mission.

The NASA Mars 2020 Perseverance Rover Mission has collected samples of rock, regolith, and atmosphere within the Noachian-aged Jezero Crater, once the site of a delta-lake system with a high potential for habitability and biosignature preservation. Between sols 109 and 1,088 of the mission, 27 sample tubes have been sealed, including witness tubes. Each sealed sample tube has been collected along with detailed documentation provided by the Perseverance instrument payload, preserving geological and environmental context.

What we can learn about Mars from the magnetism of returned samples.

The Red Planet is a magnetic planet. The Martian crust contains strong magnetization from a core dynamo that likely was active during the Noachian period when the surface may have been habitable. The evolution of the dynamo may have played a central role in the evolution of the early atmosphere and the planet's transition to the current cold and dry state.

Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.

Chemical inducers of proximity (CIPs) are molecules that recruit one protein to another and introduce new functionalities toward modulating protein states and activities. While CIP-mediated recruitment of E3 ligases is widely exploited for the development of degraders, other therapeutic modalities remain underexplored. We describe a non-degrader CIP-DNA-encoded library (CIP-DEL) that recruits FKBP12 to target proteins using non-traditional acyclic structures, with an emphasis on introducing stereochemically diverse and rigid connectors to attach the combinatorial library.

Thermogelation of nanoemulsions stabilized by a commercial pea protein isolate: high-pressure homogenization defines gel strength.

The impact of animal-based food production on climate change drives the development of plant-based alternatives. We demonstrate the use of colloidal thermogelation on a real nanoemulsion system to create structured gels that could be of interest for thermo-mechanical processing of next-generation plant-based food applications. We use a commercial pea protein isolate (PPI) without further purification to stabilize a 20 vol% peanut oil-in-water nanoemulsion at pH = 7 by high-pressure homogenization (HPH) and demonstrate the temperature induced gelation behavior of the nanoemulsion as a function of the HPH processing parameters.